Excess Mortality Attributable to Hospital-Acquired Antimicrobial-Resistant Infections: A 2-Year Prospective Surveillance Study in Northeast Thailand.

Background: Quantifying the excess mortality attributable to antimicrobial-resistant (AMR) bacterial infections is important for assessing the potential benefit of preventive interventions and for prioritization of resources. However, there are few data from low- and middle-income countries. Methods: We conducted a 2-year prospective surveillance study to estimate the excess mortality attributable to AMR infections for all types of hospital-acquired infection (HAI), and included bacterial species that were both locally relevant and included in the World Health Organization priority list. Twenty-eight-day mortality was measured. Excess mortality and population attributable fraction (PAF) of mortality caused by AMR infections compared to antimicrobial-susceptible (AMS) infections, adjusted for predefined confounders, were calculated. Results: We enrolled 2043 patients with HAIs. The crude 28-day mortality of patients with AMR and AMS infections was 35.5% (491/1385) and 23.1% (152/658), respectively. After adjusting for prespecified confounders, the estimated excess mortality attributable to AMR infections was 7.7 (95% confidence interval [CI], 2.2-13.2) percentage points. This suggests that 106 (95% CI, 30-182) deaths among 1385 patients with AMR infections might have been prevented if all of the AMR infections in this study were AMS infections. The overall PAF was 16.3% (95% CI, 1.2%-29.1%). Among the bacteria under evaluation, carbapenem-resistant Acinetobacter baumannii was responsible for the largest number of excess deaths. Among all types of infection, urinary tract infections were associated with the highest number of excess deaths, followed by lower respiratory tract infections and bloodstream infections. Conclusions: Estimating and monitoring excess mortality attributable to AMR infections should be included in national action plans to prioritize targets of preventive interventions. Clinical Trials Registration: NCT03411538.

Impact of low blood culture usage on rates of antimicrobial resistance.

OBJECTIVES: The magnitude of impact caused by low blood culture utilization on estimates of the proportions and incidence rates of antimicrobial-resistant (AMR) bacterial infections is largely unknown. METHODS: We used routine electronic databases of microbiology, hospital admission and drug prescription at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand, from 2011 to 2015, and bootstrap simulations. RESULTS: The proportions of Escherichia coli and Klebsiella pneumoniae bacteraemias caused by 3rd generation cephalosporin resistant isolates (3GCREC and 3GCRKP) were estimated to increase by 13 and 24 percentage points (from 44% to 57% and from 51% to 75%), respectively, if blood culture utilization rate was reduced from 82 to 26 blood culture specimens per 1,000 patient-days. Among patients with hospital-origin bloodstream infections, the proportion of 3GCREC and 3GCRKP whose first positive blood culture was taken within ±1 calendar day of the start of a parenteral antibiotic at the study hospital was substantially lower than those whose first positive blood culture was taken later into parenteral antibiotic treatment (30% versus 79%, p<0.001; and 37% versus 86%, p<0.001). Similar effects were observed for methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter spp. and carbapenem-resistant Pseudomonas aeruginosa. CONCLUSION: Impacts of low blood culture utilization rate on the estimated proportions and incidence rates of AMR infections could be high. We recommend that AMR surveillance reports should additionally include blood culture utilization rate and stratification by exposure to a parenteral antibiotic at the hospital.

Patient Characteristics, Management, and Predictors of Outcome from Severe Community-Onset Staphylococcal Sepsis in Northeast Thailand: A Prospective Multicenter Study.

AbstractStaphylococcus aureus infection is a persistent threat in resource-restricted settings in southeast Asia but informative data about this disease remain limited. We analyzed characteristics, management, and predictors of outcome in severely septic patients with community-onset S. aureus infection in northeast Thailand. We performed a prospective, multicenter observational cohort study of community-onset S. aureus sepsis in four referral hospitals recruiting patients at least 14 years of age admitted between March 2010 and December 2013. One hundred and nineteen patients with severe staphylococcal sepsis were enrolled. Diabetes was the most common underlying condition. Methicillin-resistant infection was rare. Twenty-eight-day mortality was 20%. Ninety-two percent of patients received appropriate antibiotic therapy and 82% were administered intravenous fluids on the first hospital day, although only 14% were managed in an intensive care unit (ICU). On univariable analysis, clinical variables at enrollment significantly associated with death at 28 days were coagulopathy or respiratory failure. Plasma interleukin (IL)-8 concentration alone accurately predicted mortality (area under the receiver operating curve = 0.82, 95% confidence interval = 0.73-0.90). In multivariable analysis, addition of IL-8 concentration to a mortality prediction model containing clinical variables further improved the predictive ability of the model. We conclude that severe staphylococcal sepsis in northeast Thailand causes significant mortality. Diabetes is a common preexisting condition and most patients are managed outside the ICU even if they receive vasoactive/inotropic agents or mechanical ventilation. While clinical factors apparent on presentation including coagulopathy and respiratory failure predict death, plasma IL-8 improves this prediction.

Increasing incidence of hospital-acquired and healthcare-associated bacteremia in northeast Thailand: a multicenter surveillance study.

BACKGROUND: Little is known about the epidemiology of nosocomial bloodstream infections in public hospitals in developing countries. We evaluated trends in incidence of hospital-acquired bacteremia (HAB) and healthcare-associated bacteremia (HCAB) and associated mortality in a developing country using routinely available databases. METHODS: Information from the microbiology and hospital databases of 10 provincial hospitals in northeast Thailand was linked with the national death registry for 2004-2010. Bacteremia was considered hospital-acquired if detected after the first two days of hospital admission, and healthcare-associated if detected within two days of hospital admission with a prior inpatient episode in the preceding 30 days. RESULTS: A total of 3,424 patients out of 1,069,443 at risk developed HAB and 2,184 out of 119,286 at risk had HCAB. Of these 1,559 (45.5%) and 913 (41.8%) died within 30 days, respectively. Between 2004 and 2010, the incidence rate of HAB increased from 0.6 to 0.8 per 1,000 patient-days at risk (p<0.001), and the cumulative incidence of HCAB increased from 1.2 to 2.0 per 100 readmissions (p<0.001). The most common causes of HAB were Acinetobacter spp. (16.2%), Klebsiella pneumoniae (13.9%), and Staphylococcus aureus (13.9%), while those of HCAB were Escherichia coli (26.3%), S. aureus (14.0%), and K. pneumoniae (9.7%). There was an overall increase over time in the proportions of ESBL-producing E. coli causing HAB and HCAB. CONCLUSIONS: This study demonstrates a high and increasing incidence of HAB and HCAB in provincial hospitals in northeast Thailand, increasing proportions of ESBL-producing isolates, and very high associated mortality.

Pediatric HIVQUAL-T: measuring and improving the quality of pediatric HIV care in Thailand, 2005-2007.

BACKGROUND: As increasing numbers of children initiate antiretroviral treatment (ART), a systematic process is needed to measure and improve pediatric HIV care quality. METHODS: Pediatric HIVQUAL-T, a model for performance measurement and quality improvement (QI), was adapted from the U.S. HIVQUAL model by incorporating Thai national guidelines as standards. In each of five pilot-site hospitals in Thailand in 2005-2007, clinical data abstracted from patient records were used to identify priority areas for QI. Improvement strategies were designed by clinic teams in different care system areas, and indicators were remeasured in 2006 and 2007. RESULTS: At the five hospitals, 1119 HIV-infected children younger than 15 years of age received care in 2005, 1183 in 2006, and 1,341 in 2007--of whom 460, 435, and 418, respectively, were selected for chart abstraction. Of the eligible children, > or = 95% received clinical monitoring, annual CD4 count monitoring, ART, and adherence and growth assessments; 60%-90% received Pneumocystis jiroveci pneumonia (PCP) prophylaxis, tuberculosis (TB) screening, oral health assessments, and HIV disclosure. Indicators with a score < or = 40% in 2005 but with significant improvement (p < .05) in 2006-2007 following QI activities were Mycobacterium avium complex (MAC) prophylaxis, and cytomegalovirus (CMV) retinitis and immunization screenings. CONCLUSIONS: Despite the promulgation of national guidelines, performance rates of some pediatric HIV indicators needed improvement. The pediatric HIVQUAL-T model facilitates use of hospital data for pediatric HIV care improvement and indicates that the U.S. HIVQUAL model is adaptable to developing countries.

Factors predicting and reducing mortality in patients with invasive Staphylococcus aureus disease in a developing country.

BACKGROUND: Invasive Staphylococcus aureus infection is increasingly recognised as an important cause of serious sepsis across the developing world, with mortality rates higher than those in the developed world. The factors determining mortality in developing countries have not been identified. METHODS: A prospective, observational study of invasive S. aureus disease was conducted at a provincial hospital in northeast Thailand over a 1-year period. All-cause and S. aureus-attributable mortality rates were determined, and the relationship was assessed between death and patient characteristics, clinical presentations, antibiotic therapy and resistance, drainage of pus and carriage of genes encoding Panton-Valentine Leukocidin (PVL). PRINCIPAL FINDINGS: A total of 270 patients with invasive S. aureus infection were recruited. The range of clinical manifestations was broad and comparable to that described in developed countries. All-cause and S. aureus-attributable mortality rates were 26% and 20%, respectively. Early antibiotic therapy and drainage of pus were associated with a survival advantage (both p<0.001) on univariate analysis. Patients infected by a PVL gene-positive isolate (122/248 tested, 49%) had a strong survival advantage compared with patients infected by a PVL gene-negative isolate (all-cause mortality 11% versus 39% respectively, p<0.001). Multiple logistic regression analysis using all variables significant on univariate analysis revealed that age, underlying cardiac disease and respiratory infection were risk factors for all-cause and S. aureus-attributable mortality, while one or more abscesses as the presenting clinical feature and procedures for infectious source control were associated with survival. CONCLUSIONS: Drainage of pus and timely antibiotic therapy are key to the successful management of S. aureus infection in the developing world. Defining the presence of genes encoding PVL provides no practical bedside information and draws attention away from identifying verified clinical risk factors and those interventions that save lives.